The status of combination therapy for visceral leishmaniasis: an updated review.

For the past 15 years, trials of combination therapy options for visceral leishmaniasis have been conducted with the aim of identifying effective, and safe treatment regimens that were shorter than existing monotherapy regimens and could also prevent or delay the emergence of drug resistance. Although first-line treatment currently relies on combination therapy in east Africa, this is not true in Latin America owing to disappointing trial results, with lower than expected efficacy seen for the combination treatment group. By contrast, several effective combination therapy regimens have been identified through trials on the Indian subcontinent; yet, first-line therapy is still AmBisome monotherapy as the drug is part of a free donation programme and is highly effective in this region. Achieving a short all-oral combination treatment will require new chemical entities, several of which are currently under evaluation. Future studies should systematically include pharmacological substudies to ensure optimal dosing for all patient groups. To achieve maximal impact of new combination treatments, mechanisms to ensure drug availability and access after trials should be established. Enhancing the longevity of current and novel treatments will require effective systems for early detection of emerging drug resistance.

Efficacy and safety of pyronaridine-artesunate (PYRAMAX) for the treatment of P. falciparum uncomplicated malaria in African pregnant women (PYRAPREG): study protocol for a phase 3, non-inferiority, randomised open-label clinical trial.

INTRODUCTION: Malaria infection during pregnancy increases the risk of low birth weight and infant mortality and should be prevented and treated. Artemisinin-based combination treatments are generally well tolerated, safe and effective; the most used being artemether-lumefantrine (AL) and dihydroartemisinin-piperaquine (DP). Pyronaridine-artesunate (PA) is a new artemisinin-based combination. The main objective of this study is to determine the efficacy and safety of PA versus AL or DP when administered to pregnant women with confirmed Plasmodium falciparum infection in the second or third trimester. The primary hypothesis is the pairwise non-inferiority of PA as compared with either AL or DP. METHODS AND ANALYSIS: A phase 3, non-inferiority, randomised, open-label clinical trial to determine the safety and efficacy of AL, DP and PA in pregnant women with malaria in five sub-Saharan, malaria-endemic countries (Burkina Faso, Democratic Republic of the Congo, Mali, Mozambique and the Gambia). A total of 1875 pregnant women will be randomised to one of the treatment arms. Women will be actively monitored until Day 63 post-treatment, at delivery and 4-6 weeks after delivery, and infants' health will be checked on their first birthday. The primary endpoint is the PCR-adjusted rate of adequate clinical and parasitological response at Day 42 in the per-protocol population. ETHICS AND DISSEMINATION: This protocol has been approved by the Ethics Committee for Health Research in Burkina Faso, the National Health Ethics Committee in the Democratic Republic of Congo, the Ethics Committee of the Faculty of Medicine and Odontostomatology/Faculty of Pharmacy in Mali, the Gambia Government/MRCG Joint Ethics Committee and the National Bioethics Committee for Health in Mozambique. Written informed consent will be obtained from each individual prior to her participation in the study. The results will be published in peer-reviewed open access journals and presented at (inter)national conferences and meetings. TRIAL REGISTRATION NUMBER: PACTR202011812241529.

Radio science results during the NEAR-shoemaker spacecraft rendezvous with eros

We determined the mass of asteroid 433 Eros, its lower order gravitational harmonics, and rotation state, using ground-based Doppler and range tracking of the Near Earth Asteroid Rendezvous (NEAR)-Shoemaker spacecraft and images of the asteroid's surface landmarks. The mass of Eros is (6.687 +/- 0.003) x 10(18) grams, which, coupled with our volume estimate, implies a bulk density of 2. 67 +/- 0.03 grams per cubic centimeter. The asteroid appears to have a uniform density distribution. The right ascension and declination of the rotation pole are 11.37 +/- 0.05 and 17.22 +/- 0.05 degrees, respectively, and at least over the short term, the rotation state of Eros is stable with no measurable free precession of the spin pole. Escape velocities on the surface vary from 3.1 to 17.2 meters per second. The dynamical environment of Eros suggests that it is covered with regolith and that one might expect material transport toward the deepest potential wells in the saddle and 5.5-kilometer crater regions.

Estimating the mass of asteroid 433 eros during the NEAR spacecraft flyby

The Near Earth Asteroid Rendezvous (NEAR) spacecraft flew within 3830 kilometers of asteroid 433 Eros on 23 December 1998. The gravitational perturbation on NEAR was evident in the spacecraft tracking data. Ground-based Doppler and range tracking of the spacecraft as well as spacecraft images of the asteroid's center of figure and surface features were used to determine the mass and rotation pole of Eros. The mass of Eros is (7.2 +/- 1.8) x 10(18) grams and, coupled with a volume estimate provided by the NEAR imaging team, this mass suggests a bulk density of 2.5 +/- 0.8 grams per cubic centimeter. The rotation pole position is 15.6 (+/-3.7) degrees in right ascension and 16.4 (+/-1.8) degrees in declination, which is consistent with ground-based and NEAR imaging team observations.

The formation of Jupiter's faint rings

Observations by the Galileo spacecraft and the Keck telescope showed that Jupiter's outermost (gossamer) ring is actually two rings circumscribed by the orbits of the small satellites Amalthea and Thebe. The gossamer rings' unique morphology-especially the rectangular end profiles at the satellite's orbit and the enhanced intensities along the top and bottom edges of the rings-can be explained by collisional ejecta lost from the inclined satellites. The ejecta evolves inward under Poynting-Robertson drag. This mechanism may also explain the origin of Jupiter's main ring and suggests that faint rings may accompany all small inner satellites of the other jovian planets.